tbuckley/cabot-search huggingface dataset:
Abstract 10181: Impact of Modified H2FPEF Score on Chronic Limb Threatening Ischemia in Patients With Lower Extremity Artery Disease Who Underwent Endovascular Therapy
Authors: Taku Shikama, yoichiro Otaki, Tetsu Watanabe, Tasuku Kurokawa, Naoaki Hashimoto, Masahiro Wanezaki, daisuke kutsuzawa, Harutoshi Tamura, Shigehiko Kato, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, Masahumi Watanabe
Journal: Circulation (2022)

Introduction: Lower extremity artery disease (LEAD) is an arterial occlusive disease characterized by an insufficient blood supply to the lower limb arteries. The H2FPEF score, calculated using simple clinical characteristics and echocardiographic findings, has been developed to identify patients at high risk for heart failure (HF) with preserved ejection fraction. Purpose: This study aimed to assess the impact of modified H2FPEF scores on chronic limb-threatening ischemia (CLTI) in patients with LEAD. Methods: Since the definition of obesity differs by race, we calculated the modified H2FPEF score using a body mass index &gt; 25 kg/m2 in 293 patients with LEAD who underwent their first endovascular therapy. Patients were retrospectively followed for a median follow-up period of 718 days. The primary and secondary endpoints were newly developed CLTI and composite events, including mortality due to worsening HF or rehospitalization in addition to CLTI, respectively. Results: The modified H2FPEF score significantly increased with advancing Fontaine classes. Kaplan-Meier analysis demonstrated that the highly modified H2FPEF score group (≥ 3) had a higher incidence of newly developed CLTI and composite events than the low H2FPEF score group (&lt;3). Multivariate Cox proportional hazard analysis revealed that the modified H2FPEF score was an independent predictor of newly developed CLTI and composite events after adjustment for confounding risk factors. The net reclassification index and integrated discrimination improvement were significantly improved by adding the modified H2FPEF score to the basic predictors. Conclusions: The modified H2FPEF score was associated with LEAD severity and future CLTI development, suggesting that it could be a feasible marker for patients with LEAD.
Abstract 10134: Role of Cardiac Sympathetic Nerves in Mediating the Central Nervous System Cardioprotective Effects of Leptin After Ischemia/Reperfusion Injury
Authors: Ana C Omoto, Jussara M Docarmo, Bejamin Nelson, Nikaela Aitken, Xuemei Dai, Sydney Moak, Zhen Wang, Alan J Mouton, Xuan Li, John E Hall, Alexandre A Da Silva
Journal: Circulation (2022)

We previously demonstrated that central nervous system (CNS) administration of leptin improves left ventricular (LV) function after myocardial infarction through mechanisms that are poorly understood. Increased cardiac sympathetic activity is an important compensatory mechanism to maintain cardiac output after ischemic injury, and previous studies showed that centrally-administered leptin increases sympathetic outflow to various tissues. In the present study, we tested the hypothesis that leptin’s CNS-mediated cardioprotective effects are mediated via cardiac sympathetic nerves. Male and female Wistar rats (~8 weeks of age) were submitted to cervical ganglia denervation (CGx) and instrumented with an intracerebroventricular (ICV) cannula in the brain lateral ventricle. After recovery and baseline assessment of cardiac function by echocardiography (ECHO) and an exercise performance test (Vmax), myocardial ischemia/reperfusion (I/R) was induced by temporary (60 min) ligation of the left anterior descending coronary artery. Vehicle (saline, 0.5 μL/hr) or leptin (0.62 μg/hr) was infused chronically for 28 days starting 20 min after reperfusion using osmotic pumps implanted subcutaneously in the scapular region and connected to the ICV cannula. Cardiac function was assessed weekly by ECHO. At the end of week 4, a final Vmax was performed and +dP/dt max was accessed by LV catheterization using a Millar catheter. Despite ~70% reduction in cardiac tyrosine hydroxylase positive fibers compared to sham, CGx did not prevent leptin’s CNS-mediated cardioprotective effects as indicated by improved ejection fraction (55±1 vs. 29±3 %), global longitudinal strain (-19±2 vs. -3±2 %), +dP/dt max (10214±614 vs. 7174±716 mmHg/s) and exercise performance (1.3±14 vs. -46.3±14 Δ% compared to baseline before I/R) when compared with CGx vehicle-treated animals. CGx also did not prevent the effect of ICV leptin to reduce septal collagen deposition and heart weight/tibia length post-I/R. These results suggests that leptin, via its CNS actions, improves cardiac function and remodeling after I/R injury independent of cardiac sympathetic innervation.
Abstract 10611: Inhibition of Sars-cov-2 Viral Channel Activity Using FDA-Approved Channel Modulators Independent of Variants
Authors: Hangang Yu, Gina Sizemore, Ivan Martinez, Peter Stoilov, Peter Perrotta
Journal: Circulation (2022)

Introduction: SARS-CoV-2 has undergone mutations, yielding clinically relevant variants such as Delta and Omicron. Early detection of virus and effective therapeutic treatment independent of variants help control virus spread. Hypothesis: We hypothesized that in the genome of SARS-CoV-2 two highly conserved viroporins Orf3a and E channels directly related to virus replication may be explored as a target for detection and inhibition of viral replication independent of variants using FDA-approved ion channel modulators. Methods: A combination of a fluorescence potassium ion assay with three channel modulators (4-aminopyridine, emodin-Orf3a channel blocker, gliclazide-E channel blocker) in a 96-well plate format was developed to detect SARS-CoV-2 Orf3a/E channel activity. We subtracted the fluorescence signals in the absence and presence of emodin/gliclazide to detect Orf3a and E channel activity. Two FDA-approved drugs, amantadine (an antiviral) and amitriptyline (an antidepressant) that are also ion channel blockers, were used to test whether they can inhibit Orf3a/E channel activity in isolated virus (UV inactivated) and in nasal swab samples from Covid-19 patients. Twenty-one (21) Delta and thirty (30) Omicron nasal swab samples were used. Variants were confirmed by PCR sequencing. Results: Orf3a and E form non-voltage-gated ion channels that are highly conserved in SARS-CoV-2 variants. In UV-inactivated SARS-CoV-2 Alpha, Beta, and Delta variants, significant channel activity of Orf3a/E was detected based on an increase in fluorescence induced by 4-aminopyridine, and this increase in fluorescence was inhibited by emodin and gliclazide (IC 50 = 0.42mM). Amantadine and amitriptyline can inhibit Delta virus with amitriptyline being a more potent inhibitor than amantadine. In swab samples of Delta variants, both amitriptyline and amantadine inhibited the channel activity of viral proteins with IC 50 values of 0.73mM and 1.11mM, respectively. In swab samples of Omicron variants, amitriptyline inhibited the channel activity with an IC 50 of 0.76mM. Conclusions: We developed an efficient method to screen FDA-approved ion channel modulators that can be repurposed to inhibit SARS-CoV-2 viral replication independent of variants.
Abstract 10176: Rate Control versus Catheter Ablation for Heart Failure Patients With Atrial Fibrillation: A Meta-Analytic Comparison
Authors: Mustafa Alam, Omar Javed Baqal, Sunny Jhamnani
Journal: Circulation (2022)

Introduction: Atrial fibrillation (AF) remains a significant cause of morbidity and mortality in the United States. Optimal management of AF in heart failure (HF) patients remains a controversy. Recent studies have demonstrated favorable outcomes of catheter ablation versus medical therapy. The purpose of this meta-analysis is to investigate whether catheter ablation achieves better outcomes as compared to rate control. Methods: A systematic search of MEDLINE was conducted using PRISMA guidelines with the search terms “rate control”, “atrial fibrillation”, and “ablation.” Studies were included if they compared a catheter ablation strategy versus rate control medical therapy in HF patients. Multiple endpoints were extracted from the articles including LVEF, 6MWD, change in BNP, and Quality of Life (QoL) outcomes using the Cochrane manual. Revman 5.4 was used to aggregate the outcomes and compute statistics using a random effects model to create forest plots. Results: A total of 7 studies with 1065 patients were included in this analysis. LVEF increased by 5.69% [4.80, 6.58] p&lt;0.00001, 6MWD increased by 24.82m [2.69, 46.94] p=0.03, BNP decreased -102.54 [-174.68, -30.40] p=0.005, and QoL outcomes using the MLHFQ improved -8.10 [-15.73, -0.48] p=0.04. Conclusions: Catheter ablation improves outcomes in HF patients with atrial fibrillation as compared to a rate control only strategy. Further large-scale randomized studies are needed to quantify improvements in outcomes.
Abstract 10070: Valve-in-Valve Transcatheter Mitral Valve Replacement versus Redo Surgical Mitral Valve Replacement-Sytemetaic Review and Meta-Analysis
Authors: Salman Zahid, Arslan Inayat, Abdallah Hamayel, Fnu Salman, Deeptanshu Jain, Omama Humayun, SAMI WARRAICH, Sachin S. Goel
Journal: Circulation (2022)

Introduction: Data on comparative outcomes between valve in valve transcatheter mitral valve replacement (ViV-TMVR) versus redo-surgical mitral valve replacement (SMVR) for degenerated bioprosthetic valves remain limited. Hypothesis: ViV TMVR is associated with lower in-hospital mortality and complication rates compared with redo SMVR. Methods: The MEDLINE (PubMed, Ovid) and Cochrane databases were queried with various combinations of medical subject headings (MeSH) to identify relevant articles. Eight studies evaluating comparative outcomes (ViV TMVR vs Redo SMVR) for patients with degenerated bioprosthetic valves were included in the analysis. Results: A total of 5,161 patients with degenerated prosthetic mitral valves underwent ViV TMVR (n = 1163) and redo SMVR (n = 3998) were included in the study. The mean age of patients was 76 versus 66 years for ViV TMVR versus the redo SMVR group, respectively (p&lt;0.01). In terms of comorbidities, female gender (55% vs 53.4%), serum creatinine (1.52 vs 1.3), dialysis (6.4% vs 6.6% ), LVEF (55.56+/-9.5 vs 57.35+/-8.7), diabetes (20.2% vs 19.5%), hypertension (73.5% vs 63.4%), atrial fibrillation (64.5% vs 69% ), and mitral regurgitation (82.4% vs 80.5%) were similar between the ViV TMVR and redo SMVR groups respectively. Using a pooled analysis, in-hospital mortality, and major bleeding were significantly lower for patients undergoing ViV TMVR compared with redo SMVR. No significant difference was observed in the incidence of stroke. The length of stay was significantly lower in the ViV TMVR group compared with the redo SMVR group. Conclusions: ViV TMVR is associated with lower in-hospital mortality, complications, and length of hospital stay compared with redo SMVR for degenerated bioprosthetic valves.
Abstract 10982: A Novel Index of Coronary Artery Calcium Derived From Preoperative Non-Gated Chest Computed Tomography Correlates With Traditional Estimates of Perioperative Risk
Authors: Samuel D Maidman, Daniel Choi, Dena Hayes, Nehal Dhaduk, Robert Donnino, Nathaniel R Smilowitz
Journal: Circulation (2022)

Introduction: Cardiovascular events are feared complications of non-cardiac surgery. Prior studies demonstrate associations between coronary artery calcium (CAC) from ECG-gated computed tomography (CT) imaging and perioperative major adverse cardiac events. We sought to evaluate correlations between an index of CAC severity from preoperative non-gated CT imaging and traditional estimates of perioperative risk. Methods We identified consecutive adults age ≥45 years who underwent in-hospital, major non-cardiac surgery across a large urban health system between 2016 and 2020 and had non-gated (contrast or non-contrast) chest CT imaging performed within 1 year prior to surgery. Patients with prior coronary revascularization or heart valve surgery were excluded. CAC severity in each coronary artery was assessed and graded from absent to severe using a 0-3 scale by physicians blinded to clinical data. An index of CAC was computed as the sum of the scores for each coronary artery. The Revised Cardiac Risk Index (RCRI) was determined for each patient. Correlations between the CAC index and RCRI were assessed using Spearman Correlation Coefficient (𝜌;). Results A total of 2,560 patients met inclusion criteria - mean age 68.1 ± 12.3 years, 49.8% female, 60% white (Figure 1A). The median pre-operative RCRI score was 1 [IQR 0-1, range 0-6] (Figure 1B). A majority of patients (64.3%) had non-contrast chest CT imaging. The median CAC index was 1 [IQR 0-3, range 0-9] (Figure 1C). A correlation between the CAC index and RCRI (Coefficient (𝜌;): 0.209, p&lt;0.001) was observed, with stepwise increases in the CAC index when stratified by pre-operative RCRI (Figure 1D). Conclusions A pragmatic, novel index of CAC derived from existing non-gated chest CT imaging correlates with pre-operative RCRI. As the RCRI is a validated preoperative risk stratification tool, this finding demonstrates the potential to leverage pre-existing, non-gated CT imaging to inform preoperative risk assessment.
Abstract 10113: Validation of a Deep-Learning-Based Retinal Biomarker in the Prediction of Cardiovascular Disease: Data From UK Biobank
Authors: Rachel M Tseng, Tyler Hyungtaek Rim, Eduard Shantsila, Sung Ha Park, Sung Soo Kim, Chan Joo Lee, Yih Chung Tham, Sahil Thakur, Joseph Yi, Simon Nusinovici, Qingsheng Peng, Marco Yu, Geunyoung Lee, Ameet Bakhai, Paul Leeson, Gregory Lip, Tien Y Wong, Ching-Yu Cheng
Journal: Circulation (2022)

Introduction: Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, with a benchmark of 10% for 10-year CVD risk determining clinical intervention. Yet, effects on clinical practice are limited and the barriers call for a simple, non-invasive risk stratification tool. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aimed to further validate our biomarker, Reti-CVD, 1) to detect risk group of ≥10% in 10-year CVD risk and 2 ) enhance risk assessment in individuals with QRISK3 of 7.5%-10% (termed as borderline-QRISK3 group) using the UK Biobank. Methods: RetiCVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of RetiCVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding RetiCVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups. Results: Among 45,233 participants with no history of CVD, 6.7% had CVD events during the 11-year follow-up. RetiCVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.34 (95% confidence interval [CI], 1.26-1.42) with a 14.7% (95% CI, 13.6-15.9%) 10-year CVD risk in RetiCVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in RetiCVD-high-risk group (12.8% in non-statin cohort [n=16240], 11.5% in stage 1 hypertension cohort [n=5102], and 14.9% in middle-aged cohort [n=11,474]). C statistics increased by 0.013 (0.010-0.017) in non-statin cohort, 0.017 (0.010-0.024) in stage 1 hypertension cohort, and 0.022 (0.017-0.027) in middle-aged cohort for CVD event prediction after adding RetiCVD to QRISK3. Conclusion: RetiCVD has the potential to identify individuals with ≥10% 10-year CVD risk who are likely to benefit from earlier, upstream preventative CVD interventions. For borderline-QRISK3 individuals, RetiCVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in early vulnerable adult groups.
Abstract 10097: Clinical Presentations and Outcomes of Atherosclerotic Cardiovascular Disease With and Without Underlying Clonal Hematopoiesis
Authors: Esra Gumuser, Zachary A Sporn, Kaavya Paruchuri, Md Mesbah Uddin, Abhishek Niroula, Benjamin Ebert, Pradeep Natarajan, Michael Honigberg
Journal: Circulation (2022)

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of hematopoietic stem cells harboring a leukemogenic mutation without blood cancer, is associated with accelerated atherosclerosis in large datasets. The clinical impact of underlying CHIP mutations on clinical presentation and outcomes among those with atherosclerotic cardiovascular disease (ASCVD) events is unknown. Methods: We included patients in the Mass General Brigham Biobank with available whole exome sequences who experienced a first ASCVD event (coronary artery disease [CAD], cerebrovascular, or peripheral artery event) following or within 6 months before blood sample collection. Individuals with CHIP (variant allele fraction &gt;2%) were matched 1:2 with CHIP-free patients by qualifying ASCVD subtype, age, sex, race, current/former smoking, and type 2 diabetes. Clinical characteristics, management, and subsequent outcomes were abstracted by chart review. Results: The sample (N=120) included 40 individuals with and 80 without CHIP (overall mean age 64.1 years), of whom 99 (82.5%) had CAD as the qualifying event. The most common CHIP drivers were DNMT3A (32.5%), TET2 (30.0%), and PPM1D (15.0%). Median (IQR) calculated 10-year ASCVD risk was 13.4% (6.9-19.5%) in those with CHIP vs. 15.5% (9.6-22.7%) in those without. Among individuals with CAD, burden of obstructed major coronary arteries on angiography was unexpectedly lower in those with CHIP (P=0.04), as were rates of revascularization. Over a median 4.1 years of follow-up after the index event, the composite of acute coronary syndrome, stroke, peripheral artery disease, and mortality occurred in 35.0% with CHIP vs. 25.0% without (P=0.29), including in 50.0% with PPM1D, 33.3% with TET2, and 23.1% with DNMT3A CHIP. Conclusions: CHIP may be prognostic among those with ASCVD events. Future larger studies should characterize mechanisms of first and recurrent events and heterogeneity across CHIP subtypes.
Abstract 10071: Myocarditis in SARS-CoV-2 Infection versus COVID-19 Vaccination: A Systematic Review and Meta-Analysis
Authors: Navya Voleti, Paddy Ssentongo
Journal: Circulation (2022)

Introduction: COVID-19 infection and vaccines are associated with acute myocarditis. However, the relative risk of myocarditis is not fully characterized. The aim of this study is to compare the risk ratio (RR) of myocarditis in COVID-19 vaccines and SARS-CoV-2 infection groups and to delineate the effect modifiers. Hypothesis: Risk ratio of myocarditis is higher in the infection group than in the vaccinated group, and this risk is modified by age and sex. Methods: Multiple electronic databases and trial registries were searched to April 2022, for randomized controlled trials and observational cohort studies reporting the risk of myocarditis associated with the COVID-19 vaccines and the risk associated with SARS-CoV-2 infection. We estimated the effect of COVID-19 infection and vaccines on rates of myocarditis by random-effects meta-analyses using the generic inverse variance method. Meta-regression analyses were conducted to assess the effect of sex and age on the incidence of myocarditis. Results: 22 eligible studies consisting of 55.5 million in the vaccinated cohort and 2.5 million in the infection cohort were included. Median age was 49 years (interquartile range (IQR): 38-56), and 49% (IQR: 43% to 52%) were male. Of patients diagnosed with myocarditis, 3.48% were hospitalized and 0.05% died. The RR for myocarditis in the infection group was15 (95% CI: 11.09 - 19.81) and 2.0 (95% CI: 1.44-2.65) in the vaccine group. Of patients who developed myocarditis after receiving the vaccine or having the infection, 61% (IQR: 39% -87%) were male. Meta-regression analysis indicated that male sex and young age were associated with myocarditis. Risk of bias assessment was moderate. Conclusions: In this systematic review and meta-analysis, we found that the risk of incident myocarditis is about 7 times higher in persons who were infected with SARS-CoV-2 virus than in those who received the vaccine.
Abstract 10865: Reduced Right Atrial Strain is a Marker for Increased Mortality in Patients With Acute Pulmonary Embolism
Authors: Shunsuke Eguchi, Michael Pfeiffer, Brandon Peterson, Mohammed Ruzieh, Zhaohui Gao, John Boehmer, John Gorcsan, Ryan Wilson
Journal: Circulation (2022)

Introduction and Hypothesis: Evaluation of the right heart function is known to have value in assessment of patients with acute pulmonary embolism (PE). The right atrium (RA) is directly impacted by right ventricular pressures. Strain analysis is an evolving area of echocardiography, and can be applied to evaluate the RA. To date, limited studies have evaluated RA strain in the setting of PE, and we hypothesized that RA strain analysis would be prognostic of outcomes in patients with acute PE. Methods: We performed a retrospective cohort study of 177 patients with acute pulmonary embolism. Strain analysis was performed on echocardiograms completed within 48 hours of admission. Peak longitudinal RA strain was applied using TomTec®. The primary outcome was 30-day all-cause mortality and in-hospital mortality. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used for evaluation. Results: Study quality was sufficient to perform peak longitudinal RA strain analysis in 151 patients (86.8%). In-hospital mortality was 8.9% and 30-day mortality was 12.7%. Peak longitudinal RA strain was significantly reduced in patients with all-cause death up to 30 days and in-hospital death compared to survivors (30-day mortality: 20.9% ± 4.9% vs 30.7% ± 7.8%, p &lt; 0.001. In-hospital mortality: 21.1% ± 5.0% vs 30.1% ± 8.0%, p &lt; 0.001). Using ROC curves, we chose a peak longitudinal RA strain value of 26.5% (sensitivity 95%, specificity 73%) for detecting all-cause mortality up to 30 days. When dividing patients into 2 groups using this cut-off value, low peak longitudinal RA strain was associated with worse prognosis (HR 33.0, 95% CI= 4.4-248.8, p &lt; 0.001. Figure). Conclusions: RA strain have significant prognostic value in patients with acute PE, and identifying those at increased risk of death which may indicate the need for more aggressive treatment. Assessment of RA strain has promise for clinical applications.